TGF-ß prevents self-reactive B cell activation
T follicular helper (TFH) cells contribute to the establishment of humoral immunity by controlling the delivery of helper signals to activated B cells. However, TFH development must be restrained, as aberrant accumulation of these cells is associated with positive selection of self–reactive germinal center B cells and autoimmunity in both humans and mice.
Dr. Julien C. Marie, head of a Helmholtz-Inserm Unit at Lyon and member of the German Cancer Research Center (DKFZ), revealed together with his colleague Dr. Mark J. Mc Carron that TGF-ß signaling in T cells prevents TFH cell accumulation, self-reactive B cell activation, and autoantibody production.
Using mice with either T cell-specific loss of or constitutive activation of TGF-ß signaling, they demonstrated that TGF-ß signaling is required for the thymic maturation of CD44+ CD122+ Ly49+ CD8+ regulatory T cells (Tregs), which induce TFH apoptosis and thus regulate this population.
Moreover, peripheral TFH cells escaping TGF-ß control were resistant to apoptosis, exhibited high levels of the anti-apoptotic protein BCL-2, and remained refractory to regulation by CD8+ Tregs. The unrestrained accumulation of TFH cells in the absence of TGF-ß was dependent on T cell receptor (TCR) engagement and required B cells.
Together their data revealed that TGF-ß signaling restrains TFH cell accumulation and B cell-associated autoimmunity and thereby controls self-tolerance.
The Helmholtz-Inserm unit, jointly founded by the Helmholtz-Association, Inserm and the DKFZ, is full part of the tumor immunology research program of the DKFZ. It is based at the CRCL (Cancer Research Center) of Lyon, France.
Mark J. McCarron and Julien C. Marie: TGF-ß prevents T follicular helper cell accumulation and B cell autoreactivity. Journal of Clinical Investigation 2014, DOI: 10.1172/JCI76179
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